| 1,579 | 16 | 234 |
| 下载次数 | 被引频次 | 阅读次数 |
肝脏疾病已经成为当今影响人类身体健康和生活质量的重要因素，也是全球健康领域所面临的重大挑战，需要引起足够的重视。肝纤维化的进一步发展可导致肝硬化、肝癌等重症肝病。虽然许多科学研究都表明，肝纤维化早期具有可逆性，但这个逆转过程非常缓慢，甚至在并发症影响下，其逆转显得极为渺茫。因此，深入研究其发病机制并积极寻找有效药物对肝纤维化的治疗具有深刻意义。肝纤维化的病因主要包括慢性病毒性肝炎、酒精性肝病、非酒精性脂肪性肝病、胆汁淤积、寄生虫病以及自身免疫性疾病等。目前，其发病机制尚未完全明确，关键环节表现为肝星状细胞活化，并进一步转化为肌成纤维细胞。特征表现为大量细胞外基质过度增生与异常沉积，导致肝脏结构破坏和假小叶生成。同时肝纤维化伴随着多种细胞因子的紊乱与氧化应激反应等，这一过程涉及机体内多条重要的信号传导通路。在治疗肝纤维化方面，由于其复杂的发病机制，目前尚未找到确切有效的西药。而传统中医药，因其具有多靶点、辨证论治的优势，在肝脏疾病包括肝纤维化的研究与治疗方面已经取得了较为不错的进展。部分单味中药、中药复方以及中药单体在抗肝纤维化治疗中发挥了积极作用，但其抗肝纤维化具体的药理作用机制仍有待进一步探索。就肝纤维化的病因、发病机制以及中医药抗肝纤维化的研究进展进行了综述。
Abstract：Liver disease has become an important factor affecting human health and quality of life today,and it is also a major challenge in the field of global health,which needs to be paid enough attention to. The further development of liver fibrosis may lead to severe liver diseases such as liver cirrhosis and liver cancer. Although many scientific studies have shown that liver fibrosis is reversible in the early stage,this process is very slow,even extremely impossible under the influence of complications. Therefore,it is of great significance to study its pathogenesis deeply and search for effective drugs for treating liver fibrosis actively.The causes of liver fibrosis mainly include chronic viral hepatitis,alcoholic liver disease,non-alcoholic fatty liver disease,cholestasis,parasitic diseases,and autoimmune diseases.At present,the pathogenesis of liver fibrosis has not been understood completely. Its key link is the activation of hepatic stellate cells, which are further transformed into myofibroblasts. It is characterized by excessive proliferation and abnormal deposition of a large amount of extracellular matrix,resulting in the destruction of liver structure and the formation of pseudolobules. Meanwhile,it is accompanied by the disturbance of various cytokines and oxidative stress,which involves many important signal transduction pathways in the body. For treating liver fibrosis,no exact and effective western medicine has yet been found due to its complex pathogenesis. Traditional Chinese medicine has made relatively good progress in the research and treatment of liver diseases, including liver fibrosis,because of its advantages of multiple targets and syndrome differentiation. Some single traditional Chinese medicines,compounds,and monomers have played a positive role in treating liver fibrosis,but the extensional pharmacological mechanism of their anti-liver fibrosis remains to be further explored. This paper reviews the etiology and pathogenesis of liver fibrosis and the research progress of traditional Chinese medicine in anti-liver fibrosis.
[1]PAROLA M,PINZANI M.Liver fibrosis:pathophysiology,pathogenetic targets and clinical issues[J].Molecular Aspects of Medicine,2019,65:37-55.
[2]范灵芝，王晓忠.中医药抗肝纤维化治疗最新研究进展[J].新疆中医药，2018,36(1):147-151.
[3]ROEHLEN N,CROUCHET E,BAUMERT T F.Liver fibrosis:mechanistic concepts and therapeutic perspectives[J].Cells,2020,9(4):875.
[4]王永林.肝纤维化的病因病机与中医药治疗初探[J].现代中西医结合杂志，2011,20(36):4693-4694.
[5]SARACCO G M,MARZANO A,RIZZETTO M.Therapy of chronic viral hepatitis:the light at the end of the tunnel?[J].Biomedicines,2022,10(3):534.
[6]BOULAHTOUF Z,VIRZìA,BAUMERT T F,et al.Signaling induced by chronic viral hepatitis:dependence and consequences[J].Int J Mol Sci,2022,23(5):2787.
[7]PATEL R,MUELLER M.Alcoholic liver disease[M].Treasure Island:StatPearls Publishing LLC,2022.
[8]KUDARAVALLI P,JOHN S.Nonalcoholic fatty liver[M].Treasure Island:StatPearls Publishing LLC,2022.
[9]XIONG X L,DING Y,CHEN Z L,et al.Emodin rescues intrahepatic cholestasis via stimulating FXR/BSEP Pathway in promoting the canalicular export of accumulated bile[J].Front Pharmacol,2019,10:522.
[10]DING H,YANG X,TIAN J,et al.JQ-1 Ameliorates schistosomiasis liver fibrosis by suppressing JAK2and STAT3 activation[J].Biomed Pharmacother,2021,144:112281.
[11]LIM Y S,OH H B,CHOI S E,et al.Susceptibility to type 1 autoimmune hepatitis is associated with shared amino acid sequences at positions 70-74 of the HLA-DRB1 molecule[J].Journal of Hepatology,2008,48(1):133-139.
[12]BAO Y L,WANG L,PAN H T,et al.Animal and organoid models of liver fibrosis[J].Front Physiol,2021,12:666138.
[13]HERNANDEZ-GEA V,FRIEDMAN S L.Pathogenesis of liver fibrosis[J].Annual Review of Pathology,2011,6:425-456.
[14]TESTERINK N,AJAT M,HOUWELING M,et al.Replacement of retinyl esters by polyunsaturated triacylglycerol species in lipid droplets of hepatic stellate cells during activation[J].PLoS One,2012,7(4):e34945.
[15]SEKI E,SCHWABE R F.Hepatic inflammation and fibrosis:functional links and key pathways[J].Hepatology,2015,61(3):1066-1079.
[16]WANG R C,WU G L,DAI T T,et al.Naringin attenuates renal interstitial fibrosis by regulating the TGF-β/Smad signaling pathway and inflammation[J].Exp Ther Med,2021,21(1):66.
[17]GUO H F,GERMAN P,BAI S S,et al.The PI3K/AKT pathway and renal cell carcinoma[J].J Genet Genomics,2015,42(7):343-353.
[18]WANG J C,HU K L,CAI X Y,et al.Targeting PI3K/AKT signaling for treatment of idiopathic pulmonary fibrosis[J].Acta Pharm Sin B,2022,12(1):18-32.
[19]吴灿，黄亮，莫立乾，等.丹参多酚酸盐通过TGF-β1/Smad和PI3K/AKT/mTOR信号通路抑制大鼠肝纤维化的进展[J].中国医院药学杂志，2019,39(7):670-675.
[20]WANG R,SONG F X,LI S N,et al.Salvianolic acid A attenuates CCl4-induced liver fibrosis by regulating the PI3K/AKT/mTOR,Bcl-2/Bax and caspase-3/cleaved caspase-3 signaling pathways[J].Drug Des Devel Ther,2019,13:1889-1900.
[21]LIU C M,ZHENG G H,MING Q L,et al.Protective effect of quercetin on lead-induced oxidative stress and endoplasmic reticulum stress in rat liver via the IRE1/JNK and PI3K/Akt pathway[J].Free Radic Res,2013,47(3):192-201.
[22]GE M,YAO W F,YUAN D D,et al.Brg1-mediated Nrf2/HO-1 pathway activation alleviates hepatic ischemia-reperfusion injury[J].Cell Death Dis,2017,8(6):e2841.
[23]FAN J,CHEN Q S,WEI L W,et al.Asiatic acid ameliorates CCl4-induced liver fibrosis in rats:involvement of Nrf2/ARE,NF-κB/IκBα,and JAK1/STAT3 signaling pathways[J].Drug Des Devel Ther,2018,12:3595-3605.
[24]徐列明，刘平，沈锡中，等.肝纤维化中西医结合诊疗指南（2019年版）[J].中国中西医结合杂志，2019,39(11):1286-1295.
[25]CHEN Z,XU H.Anti-inflammatory and immunomodulatory mechanism of tanshinone IIA for atherosclerosis[J].Evidence-Based Complementary and Alternative Medicine,2014,2014:267976.
[26]JUNG I,KIM H,MOON S,et al.Overview of salvia miltiorrhiza as a potential therapeutic agent for various diseases:an update on efficacy and mechanisms of action[J].Antioxidants(Basel),2020,9(9):857.
[27]刘雪梅，张园，韦燕飞.桂莪术提取物对人肝星状细胞的影响[J].世界科学技术-中医药现代化，2014,16(4):780-783.
[28]雷玲，闵珺，刘锋，等.黄芪对肝纤维化大鼠肝损伤保护作用及机制研究[J].陕西中医，2020,41(9):1192-1196.
[29]吴硕.扶正化瘀方对肝纤维化小鼠肝细胞中Nrf2表达的影响[D].济南：山东大学，2013.
[30]聂红明，王灵台.安络化纤丸抗肝纤维化的研究进展[J].中西医结合肝病杂志，2016,26(3):185-187.
[31]卢玮，高玉华，王珍子，等.安络化纤丸对肝纤维化大鼠转化生长因子β1及相应信号通路的影响[J].中华肝脏病杂志，2017,25(4):257-262.
[32]刘世政，凌再芹，林爱清.小柴胡汤通过TGF-β1/Smad通路改善大鼠肝纤维化[J].中南医学科学杂志，2021,49(1):58-62.
[33]YING Q J,TENG Y Y,ZHANG J,et al.Therapeutic effect of tanshinone IIA on liver fibrosis and the possible mechanism:a preclinical meta-analysis[J].Evid Based Complement Alternat Med,2019:7514046.
[34]SHU M,HU X R,HUNG Z A,et al.Effects of tanshinone IIA on fibrosis in a rat model of cirrhosis through heme oxygenase-1,inflammation,oxidative stress and apoptosis[J].Mol Med Rep,2016,13(4):3036-3042.
[35]CHE X H,PARK E J,ZHAO Y Z,et al.Tanshinone IIA induces apoptosis and S phase cell cycle arrest in activated rat hepatic stellate cells[J].Basic Clin Pharmacol Toxicol,2010,106(1):30-37.
[36]王诗洋，王枭，徐祖清，等.苦杏仁苷通过抑制氧化应激及炎症反应减轻四氯化碳诱导的大鼠肝纤维化作用[J].现代免疫学，2020,40(6):471-475,481.
[37]俞泽元，王科深，任彦先，等.姜黄素抗胰腺癌的作用机制[J].临床肝胆病杂志，2018,34(4):900-904.
[38]KONG D S,ZHANG F,SHAO J J,et al.Curcumin inhibits cobalt chloride-induced epithelial-to-mesenchymal transition associated with interference with TGF-β/Smad signaling in hepatocytes[J].Laboratory Investigation,2015,95(11):1234-1245.
基本信息:
DOI：10.16389/j.cnki.cn42-1737/n.2023.03.008
中图分类号:R285
引用信息:
[1]李青青,杨红胜,李金斗,等.肝纤维化发病机制及中医药抗肝纤维化的研究进展[J].江汉大学学报(自然科学版),2023,51(03):75-81.DOI:10.16389/j.cnki.cn42-1737/n.2023.03.008.
基金信息:
湖北省中医药管理局中医药科研项目（ZY2023F142）; 国家级大学生创新创业训练计划项目（202211072004）; 湖北省级大学生创新创业训练计划项目（S202211072027）; 江汉大学大学生科研重点项目（2022zd053,2022zd059）
2023-06-06
2023-06-06